Depletion of adherent cells causes decreased synthesis of DNA by normal rat lymph node cells (LNC) stimulated with phytohemagglutinin (PHA). Purified peritoneal (PE) macrophages restore normal reactivity to low doses of PHA but depress the reaction at higher PHA levels or at higher macrophage concentrations (5%). With spleen cells, removal of adherent cells results in a marked increase of the response, and the addition of PE macrophages does not return it to the normal level. Spleen cells also show a clear-cut inhibition of thymidine incorporation at cell concentrations greater than 1 × 106/ml. This “suppressor” effect disappears when adherent cells are removed, resulting in a linear dose-response curve with increasing cells similar to that of LNC. The existence of an adherent suppressor cell distinct from the macrophage is therefore postulated.